The specific binding of low-density lipoprotein (LDL) to cells and its subsequent uptake into these cells is well documented, but little is known of the LDL binding and uptake by skeletal muscle. Lipoproteins are the major transporters of tocopherols, deficiencies of which have been associated with a number of muscle diseases of animals. Their possible implication in human muscle diseases prompted our investigation of LDL and high-density lipoprotein (HDL) binding and uptake into human muscle cells in culture. Cultured human muscle cells were used at both the myoblast and myotube stage. They were incubated with LDL or HDL which were labelled by protein iodination or with (3H) alpha-tocopherol and receptor binding and cell uptake characteristics established. LDL binds to both myoblasts and myotubes, but the binding affinity increases significantly with the more highly differentiated cells. This binding appears to be specific to LDL receptors. The LDL is taken into the muscle cell and protein is degraded, as with other types of cells. HDL also binds to muscle cells, but there is no evidence of internalization. alpha-Tocopherol is transferred to muscle cells from both LDL and HDL, but the transfer is not dependent on lipoprotein internalization. HDL is effective as a means of transport of alpha-tocopherol to muscle cells, but LDL appears to be about one order more effective.